British fournal of Dermatology {\993) 128, 633-635.

Transepidermal water loss and absorption of

hydrocortisone in widespread dermatitis
K.AALTO-KORTE AND M.TURPEINEN
Department of Skin and Allergic Diseases. University Central Hospital. Meilahdentie 2. 002$0 Helsinki, Finland
Accepted for publication 28 November 1992

Summary Percutaneous absorption of hydrocortisone was measured in three children and six adults with
widespread dermatitis, after the application of 1% hydrocortisone cream. Before application of the
cream, the transepidermai water loss (TEWL) was measured on six skin areas. A highly significant
correlation was found between the post-application rise in plasma cortisol levei and the mean
transepidermal water loss. Thus, measurement of TEWL affords a simple, non-invasive method for
assessing the systemic effect of hydrocortisone applied to widespread dermatitis.

Data about the permeability of damaged and diseased
skin are relatively sparse. Generally, in most injured and
diseased skin the barrier function is disturbed, and
absorption of most chemicals and drugs is increased.'
Transepidermal water loss (TEWL) reflects the barrier
function of the skin. A correlation between TEWL and
percutaneous absorption of acetylsalicylic acid, caffeine
and benzoic acid soditim salt in healthy skin has been
noted previously.-^
In active dermatitis, the skin barrier function is
disturbed and TEWL is increased. During convalescence
TEWL gradually decreases to the normal level.* Percuta-
neous absorption of hydrocortisone can be measured by
a direct method using plasma cortisol determinations
during dexamethasone suppression.** The percutaneous
absorption of hydrocortisone increases with the severity
of the dermatitis.^ In the acute phase, percutaneous
absorption of hydrocortisone is higher than during
remission in both children and adults.^^ These findings
imply a close relationship between TEWL and percuta-
neous absorption of hydrocortisone. To our knowledge,
this relationship has not been evaluated previously.
Methods
Patients
Percutaneous absorption of hydrocortisone and TEWL
were studied in three children and six adults with
dermatitis. Their ages ranged from 3 to 52 years. AU had
widespread dermatitis covering at least 60% of the total
skin area (median 90%). At the time of the absorption
test, the dermatitis was scored by grading the erythema
Correspondence: Kristiina Aalto-Korte.
and excoriations separately: 0. none: 1. mild: 2, moder-
ate; 3. severe. The sum of these scores ranged from 3 to 5
(median 4) (Table 1). All the patients or their parents
gave their informed consent.
Plasma cortisol determination
Plasma cortisol levels were determined by radioimmu-
noassay {Farmos Diagnostica, Turku, Finland). In this
test the cross-reactivity with dexamethasone is less than
0-005%.
Determination of transepidermal water loss
TEWL was measured in six standard skin areas (two on
the upper chest, two on the upper back, and two on each
forearm) immediately before application of the hydrocor-
tisone cream. Each individual TEWL value was calcu-
lated as a mean of these six measurements. AU the
measurements were performed with the same evapori-
meter (Servo Med Evaporimeter EPl, Servo Med AB,
Stockholm. Sweden). In the laboratory, the temperattire
varied between 2 1 9 and 26-5°C (median 23-7°C), and
tbe relative humidity between 19 and 45% (median
37%).
Absorption test
All the patients were hospitalized because of an exacer-
bation of their dermatitis. All therapy was discontinued,
except applications of the cream base, for at least 36 h
before the test.
633
634 K.AALTO-KORTE AND M.TURPEINEN

Table 1, Ciinicai detaiis of patients

Siiin area Amount of
affected by Scores for cream used
Patient ilMagnosis Sex/age (years) dermatitis (%) erythema/excoriations (g)

1 AD F/J 90 2/3 60
2 AD M/7 90 3/2 42
3 SD M/7 90 3/2 84
4 AD F/20 90 2/1 50
5 AD F/22 60 211 50
6 AD F/22 60 2/2 50
7 AD M/39 90 3/1 75
8 AD F/44 90 2/3 50
9 AD M/52 90 2/2 50

AD. atopic dermatitis: SD, seborrhoeic dermatitis.

Blood samples for cortisol determinations were taken

via an intravenous plastic cannula in the morning,
before, and 2 and 4 h alter, application of 1% hydrocorti-
sone cream at 08.00-09.00 h. The amount of cream
varied hetween 41 and 84 g, depending on the indi-
vidual's need for local treatment. The proprietary cream
base contained white petrolatum, macrogol 400. cetos-
tearol, cetomacrogol 1000 and methyl parahydroxy-
benzoate with 60% water. Occlusion was not used.
20 30 50 100 200 300 500 IOOO 2000
Endogenous secretion of cortisol was suppressed with
Increment in plasma cortJsol (nmol/l)
oral dexamethasone.' The dose of dexamethasone was
0-5 mg if the body surface area was between 0-5 and Figure 1. Relation between TEWL and tiie increment in plasma c ortisol
0-99 m^ 0-75 mg between 1-0 and 1-49 m-', and 1 mg in the percutaneous absorption test, in nine patients witii wide.spread
for a body surface of > 1 -S m^. All the patients received dermatitis. Logio scales bave been used to normaiize the siiewed
distributions of tbe two variables. 95% confidence limits are given. The
dexamethasone every 6 h, and the first dose was given regression ilne is: logi,, TEWL=O-39 logn, piasma cortisol + 0-51.
13-14h beforemeasurement ofthe basal cortisol value. Spearman's ranit correlation coefficient r^ is U-991 IP<O 001; 95%
Percutaneous absorption of hydrocortisone was confidence limits for r, 0 955-0-998).
expressed as the 4-h post-application increment in
plasma cortisol.''"

morning basal levels of plasma cortisol in all the patients

Statistical analysis
The relationship between TEWL and hydrocortisone
absorption was evaluated using Spearman's rank corre-
lation test. The correlation was illustrated by using
Pearson's regression analysis (Fig. 1).
The 95% confidence limits were calculated using CIA
(Confidence Interval Analysis. Gardner MJ. Altman DG,
BM] 1989).
(range < 20-66 nmol/!). The rise in plasma cortisol level
ranged from 12 to 2150 nmol/1 (Tahle 2}. The mean
TEWL ranged from 9 to 75 g/m^/h (Table 2). The skin
temperature varied between 30-2 and 341°C. The
concordance between the post-application increment in
plasma cortisol level and the mean TEWL was highly
significant. Spearman's rank correlation coefficient r^
was 0-991 (P<0-001: 95% confidence limits for r, are
O-955-O-998).

Results
The effect of adrenocortical suppression with dexa-
methasone was seen in the subnormal (<25O nmol/1)
Discussion
In addition to the primary defect of the skin barrier
caused by dermatitis. TEWL is also influenced by skin
temperature.** It is possible that the absorption of
 TEWL AND HYDROCORTISONE ABSORPTION IN DERMATITIS
Table 2. Results of TEWL measurements and the increment In plasma
cortisol in the percutaneous absorption test
Mean TEWL Increment in plasma
Patient (g/mVh) cortisol (nmol/1)
I 55 848
2 54 1006
3 75 2150
4 22 203
5 20 94
6 9 12
7 44 576
8 14 35
9 16 73
hydrocortisone. and its pharmacokinetics, are also
affected by skin temperature although, to our know-
ledge, no quantitative data are available about this
effect. The relationship between TEWL and skin tem-
perature is different in normal and eczematous skin.**
The formula for eczematous skin presented by Grice et al.
is difficult to employ because it requires TEWL readings
at two different skin temperatures.** Mathias et al. have
criticized the work of Grice's group, and their own
formula was derived from a study of normal cadaver
skin.^ We did not correct the readings of TEWL for skin
temperature, because a suitable formula for eczematous
skin is not available, and because we do not know how
the post-application increment in plasma cortisol is
influenced by skin temperature. In order to evaluate the
relationship between these two variables, both should
have been adjusted for skin temperature at the same
time.
Dexamethasone. which is used in the absorption test is
anti-inflammatory. TEWL and absorption of hydrocorti-
sone are both underestimated with this method. TEWL
was measured immediately before the absorption test.
We assume that dexamethasone does not affect the
relation between TEWL and percutaneous absorption.
Both TEWL^ and percutaneous absorption of hydro-
cortisone^'' have been found to correlate with the
clinical severity of dermatitis. In our patients with severe
and widespread dermatitis, however, interindividual
differences of several-fold were observed in both these
variables. Large differences in absorption have also been
noted previously within groups with dermatitis of
635
different grades of severity.^' This variation makes it
difficult to estimate the permeability ofthe skin barrier to
steroids by clinical means alone. In the present study, a
highly significant correlation was found between TEWL
and percutaneous absorption of hydrocortisone. High
absorption ( > 700 nmol/I) has, in turn, been found to be
associated with adrenocortical suppression.'" As a sim-
ple, non-invasive method, the measurement of TEWL
could be used in identification of patients with a high risk
of systemic side-effects from topical corticosteroid treat-
ment. Eurthermore, the regression line between TEWL
and percutaneous absorption of hydrocortisone could be
used to evaluate the effects of different cream bases and
delivery systems (e.g. Uposomes) on the pharmacokine-
tics of hydrocortisone. by measuring these two variables
at the same time.
References
1 Moon KC. Maibacii HI. Percutaneous absorption in diseased skin:
relationship lo exogenous dermatosis. In: Exogenous Dermatoses:
Environmental Dermatitis (Menne T, Maibach HI eds). Boca Raton:
CRC press. 1991: 217-24.
2 Rougier A. Lotte C, Maibach HI. In vivo relationship between
percutaneous absorption and transepidermai water loss. In:
Percutaneous Absorption IBronaugh RL. Maibach HI, eds). 2nd edn.
New York; Marcel Dekker. 1989: 182-7.
3 Shahiduiiah M. Raffle El, Rimmer AR, Frain-Bell W. Transepider-
mal water loss in patients with dermatitis. Br j Dermatol 1969; 81:
722-30.
4 TurpeinenM. SaioOP. Leisti S. Effect of percutaneous absorption of
hydrocortisone on adrenocorticai responsiveness in infants with
severe skin disease. Br J Dermatol 1986: 115: 475-84.
5 Turpeinen M. Influence of age and severity of dennatitis on the
percutaneous absorption of hydrocortisone in chiidren. Br /
i^rmatol 1988: 118: 517-22.
6 Turpeinen M. Lchtokoski-Lehtiniemi E, Leisti S, Salo OP. Percuta-
neous absorption of hydrocortisone during and after the acute
phase of dermatitis in children. Pediatr Dermatol 1988; 5: 276-9.
7 Turpeinen M. Mashkiiieyson N. Bjorksten F. Saio OP. Percuta-
neous absorption of hydrocortisone during exacerbation and
remission of atopic dermatitis in aduits. Acta Derm Venereol
(Stockh) 19S8; 68: 331-5.
8 Grice K, Sattar H, Baker H. The relationship of transepidermal
water ioss to skin temperature in psoriasis and eczema. / Invest
Dermatol 1975; 64: 313-15.
9 Mathias CGT. Wilson DM, Maibach HI. Transepidermai water loss
as a function of skin surface temperature. / Invest Dermatol 1981:
77:219-20.
10 Turpeinen M. Adrenocortical response to adrenocorticotropic
hormone in relalion to duration of topical therapy and percuta-
neous absorption of hydrocortisone in chiidren with dermatitis.
Eur } Pediatr 1989; 148: 729-31.